No one appreciates controversy for its own sake. We have an expression for a person who argues for no reason other than generating debate by taking a different viewpoint: devil’s advocate.

In today’s world, it often has a negative implication. It’s a bad feeling when we sense someone is only trying to win for the sake of their ego, or whatever. But playing devil’s advocate wasn’t always bad. In fact, during the Middle Ages, a lawyer or other scholar could be appointed as a Devil’s Advocate to weed out false evidence. It was an important role, designed to make sure one side in a controversy did not have too much power. Assuming, of course, that the points made on each side were logical and rational.

Is Gleason 6 really cancer?

In other words, discussion and debate are healthy when the sides are balanced—even to the point of being hard to choose a clear outcome. In the world of prostate cancer (PCa), we are in the midst of a similar situation. The issue is Gleason 6 (3+3) prostate cancer REALLY cancer?

An October 1, 2024 medical news story opens, “A new paper in the Journal of the National Cancer Institute, published by Oxford University Press, indicates that patients may benefit if doctors stop calling certain early-stage changes to the prostate ‘cancer’ at all.” While this may seem startling, it may help to bring about a change that benefits patients.

The paper in question, written by a panel of experts including Dr. Matthew Cooperberg, is titled “When is prostate cancer really cancer?”^[i] How do you define “really”? You see, there are benign (noncancerous) tumors and malignant (cancerous) tumors, and they don’t behave the same. Benign tumors may grow in size, but unlike cancer, they don’t aggressively spread to other parts of the body. That trait, called metastasis, is what we all truly fear when we hear the word cancer. That disease conjures up images of a sneaky enemy forming colonies throughout the body, bringing suffering and death to their host. Scary!

The current controversy over what to call Gleason 6 PCa concerns all early changes in prostate cells. Will they all end up behaving like cancer? This question is raised by increasingly sophisticated scientific cell analysis at the molecular level. Instead of clear-cut identification (i.e., this cell is cancer but that is not), researchers are finding what the authors call “a continuum of genomic changes” in gene variants. They are trying to figure out which are associated with truly aggressive spread. Simply put, there are a LOT of cells that look like early PCa (Gleason grade 3+3 = 6, or Grade Group GG1), but they will probably never become truly malignant. The Cooperberg paper states that “autopsy studies reveal GG1 is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize.”

Two viewpoints

So, if GG1 won’t behave like cancer, why bother calling it cancer? As you might imagine, the professional discussion over this issue is lively, and it boils down to two camps:

• Those in favor of keeping the name cancer: The goal of PCa detection, diagnosis and treatment is to save lives. Even if the majority of abnormal cancer-like cells remain indolent, we still have not definitively identified which genomic variants may trigger an abrupt transformation into aggressive cells, nor can we predict when that could happen. If we don’t call it cancer, patients told not to worry because their abnormal cells may never become dangerous might simply deny what’s going on in their prostate, ignore the need to monitor, and ultimately risk their lives.
• Those in favor of renaming GG1 lesions: Patients suffer from overdiagnosis and overtreatment of low-grade cells that may never need treatment, but diagnosing them as cancer triggers patient fears. Frightened patients may agree to the burden of whole gland treatment at the price of potentially compromised urinary, sexual and bowel function–even if temporarily.

Regardless of who favors which viewpoint, all agree that the objective of screening, detection, diagnosis, and treatment is to lower the rate of death due to PCa while also reducing the cost of over-diagnosis and over-treatment to patients and healthcare economies.

Thus, the issue of terminology goes unresolved. Currently, patients understand words like very low risk PCa, low risk PCa, Gleason grade 6, Grade group 1—but these still conjure up CANCER in their minds. Here are a couple of other suggested terms, but doctors may be challenged to explain to patients without using the CANCER word: incidentaloma and acinar neoplasm. What do you think? Will cancer by any other name still be as scary?

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you have health concerns or questions of a personal medical nature.

References

[i] Cooperberg MR, Braun AE, Berlin A, Kibel AS, Eggener SE; CANCER-GG1 Writing Group. When is prostate cancer really cancer? J Natl Cancer Inst. 2024 Oct 1:djae200.